Tardive dyskinesia (TD) is a serious public health problem and significant limitation of antipsychotic drug treatment. Although the condition is severe in only a relatively small proportion of TD cases, these are characterized by extreme pain and functional disability. The syndrome is often persistent and unable to be reversed by currently available treatment. Clozapine is an investigational drug with atypical properties and novel pharmacologic profile. Preliminary studies have demonstrated its antipsychotic efficacy and potential utility in treatment of TD. Based on preliminary work, we postulate that clozapine will have therapeutic efficacy in severe TD. particularly tardive dystonia. Specifically, we hypothesize that clozapine will exert a genuine therapeutic effect on the symptoms of TD which is both dose (a minimum threshold dose is required) dependent. Unlike the effect of classical neuroleptics this therapeutic effect is not merely masking symptoms but a genuine therapeutic effect that will persist after drug withdrawal. To test this hypothesis we propose to study sixty patients with severe TD who meet entry criteria and are in need of treatment. They will be admitted to the inpatient service and after a two week drug-free interval be stratified by the presence or absence of dystonia and randomly assigned to treatment with clozapine or haloperidol plus benztropine for 12 weeks under double-blind conditions. Dosage will be titrated in a standardized manner. After 12 weeks patients will be withdrawn from treatment and followed four weeks. Patients who received haloperidol will then be treated openly with clozapine as per the double-blind protocol. Patients who respond to clozapine in the double-blind or open treatment condition will be followed on clozapine for up to one year, after which medication will again be discontinued to evaluate long-term response.